Circulating miRNA in Patients Undergoing Total Pancreatectomy and Islet Autotransplantation

Srividya Vasu, Jiemin M. Yang, James Hodges, Maisam A. Abu-El-Haija, David B. Adams, Appakalai N. Balamurugan, Greg J. Beilman, Srinath Chinnakotla, Darwin L. Conwell, Martin L. Freeman, Timothy B. Gardner, Betul Hatipoglu, Varvara Kirchner, Luis F. Lara, Katherine A. Morgan, Jaimie D. Nathan, Andrew Posselt, Timothy L. Pruett, Sarah J. Schwarzenberg, Vikesh K. SinghMartin Wijkstrom, Piotr Witkowski, Bashoo Naziruddin, Melena D. Bellin

Research output: Contribution to journalArticlepeer-review

Abstract

Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples (n = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p (P = 0.03), hsa-miR-148a-3p (P = 0.04) and hsa-miR-221-3p (P = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p (P = 0.04) and hsa-miR-7-5p (P = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p (P < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p (P < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, r = 0.18; hsa-miR-148a-3p, r = 0.21; hsa-miR-320d, r = 0.19; and hsa-miR-221-3p, r = 0.21; all P < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg (r = −0.20, P = 0.02). Also, hsa-miR-200c (r = 0.18, P = 0.03) and hsa-miR-221-3p (r = 0.19, P = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.

Original languageEnglish (US)
JournalCell transplantation
Volume30
DOIs
StatePublished - Apr 28 2021

Bibliographical note

Funding Information:
M. Bellin discloses research funding from Viacyte and Dexcom, and medical advisory role (DSMB) for Insulet. The authors of this manuscript otherwise have no conflicts of interest to disclose.

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was funded by NIDDK R01-DK109124 (PI Bellin).

Publisher Copyright:
© The Author(s) 2021.

Keywords

  • biomarker
  • chronic pancreatitis
  • circulating miRNAs
  • islet transplantation

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